rs786204848

Positions:

• chr9-32488884-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_014314.4(RIGI):​c.803G>T​(p.Cys268Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIGI NM_014314.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.57

Genes affected

RIGI (HGNC:19102): (RNA sensor RIG-I) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases which are implicated in a number of cellular processes involving RNA binding and alteration of RNA secondary structure. This gene encodes a protein containing RNA helicase-DEAD box protein motifs and a caspase recruitment domain (CARD). It is involved in viral double-stranded (ds) RNA recognition and the regulation of the antiviral innate immune response. Mutations in this gene are associated with Singleton-Merten syndrome 2. [provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.818
• PP5: Variant 9-32488884-C-A is Pathogenic according to our data. Variant chr9-32488884-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 189345.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-32488884-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIGI	NM_014314.4	c.803G>T	p.Cys268Phe	missense_variant	7/18	ENST00000379883.3	NP_055129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3	c.803G>T	p.Cys268Phe	missense_variant	7/18	1	NM_014314.4	ENSP00000369213	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Singleton-Merten syndrome 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 05, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.3	.;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Pathogenic	0.74
Sift	Benign	0.043	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	.;D
Vest4		0.54
MutPred		0.76		.;Loss of ubiquitination at K270 (P = 0.1486);
MVP		0.79
MPC		0.66
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.95
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs786204848; hg19: chr9-32488882; COSMIC: COSV99060504;